This project will analyze genetically and developmentally caused variation of 2,3-diphosphoglycerate (DPG) and ATP levels of the rat and mouse red cell. The aim is to determine both the biochemical causes of the variation and the effects of this variation on red cell oxygen affinity. In the rat, the focus is on a known source of variation, in which low DPG and low ATP levels are caused by a recessive gene at a single locus. Both high-DPG/high-ATP and low-DPG/low-ATP rats will be examined in the early embryonic, fetal, young, and adult stages for red cell DPG, ATP, intracellular pH and oxygen affinity. Levels of additional red cell gylcolytic intermediates and enzyme activities will be examined in order to determine the enzymatic regulatory processes which underlie the variation in DPG and ATP. A similar sort of genetic variation is being searched for in the mouse, and a study parallel to that of the rat will be conducted. These data will aid in the understanding of biochemical mechanisms which determine red cell DPG and ATP levels and hence oxygen affinity. The study should also increase our knowledge of the functioning of red cells during mammalian embryonic and fetal life.